P859: PROGNOSTIC IMPACT OF OPIOID USE PRIOR TO DIAGNOSIS OF MULTIPLE MYELOMA
Authors: Christian Brieghel, Ólafur Davídsson, Klaus Rostgaard, Agoston Szabo, Ulf Christian Frølund, Henrik Hjalgrim, Carsten Niemann
Journal: HemaSphere (2023)

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Myeloma bone disease (MBD) is the leading cause of morbidity in multiple myeloma (MM) causing bone fracture and vertebral collapse in severe cases. Up to 80% of patients are diagnosed with MBD, and many newly diagnosed patients will have started analgesics prior to diagnosis. Opioids remain the standard of care in management of bone pain in MM and are widely used. Even so, the use opioids and their prognostic impact remain largely unstudied. Aims: To investigate the prognostic impact of prediagnostic opioid use in MM. Methods: We identified all Danish patients registered with MM in the Danish Myeloma Database (2005 through 2019) including information on age, sex, international staging system (ISS), revised ISS (R-ISS), Ca-ion and presence of MBD at time of diagnosis. Primary cancers (PC; excluding non-melanoma skin cancer) were identified through the Danish pathology register. Information on opioid prescriptions (2004 through 2019) were retrieved from the Danish prescription register using ATC codes for codeine (R05DA04), tramadol (N02AX02), pure morphine (N02AA01), oxycodone (N02AA05), buprenorphine (N02AE01), and fentanyl (N02AB03). We included prescriptions up until 3 months prior to MM diagnosis accounting for a substantial diagnostic delay. Overall survival (OS) was calculated from time of diagnosis until death or end of follow-up. We grouped patients according to an opioid analogue hierarchy in which opioids with strongest analgetic effect ranked highest. Results: Among 4692 patients with symptomatic MM, 2132 (45.4%) had a preexisting opioid use. In total, 22,271 opioid prescriptions had been filled for codeine (14.8%), tramadol (54.1%), pure morphine (8.4%), oxycodone (16.1%), buprenorphine (4.3%), and fentanyl (2.4%). Grouped according to the opioid analogue hierarchy, 224 (5.5%), 1193 (25.4%), 205 (4.4%), 341 (7.3%), 97 (2.1%) and 72 (1.5%) patients had received codeine, tramadol, pure morphine, oxycodone, buprenorphine, and fentanyl as the strongest opioid, respectively. At diagnosis, patients with a preexisting opioid use had similar occurrence of MBD (73.0% vs 74.0%, P=0.50, χ2) and similar Ca-ion levels (median 1.28 mM [IQR 1.22;1.35] vs 1.27 [1.23;1.36], P=0.43, χ2) as compared to patients with no opioid use. The yearly rate of any opioid prescription (rx per patient at risk per year) steadily increased from 0.2 to 0.8 from 15 to 2 years prior to MM diagnosis, and rapidly increased to 2.3 the last year prior to MM diagnosis. Results on when the rate of opioid prescriptions starts to exceed that of the healthy population will be presented at the meeting. With a median follow-up of 8.2 years (interquartile range 5.3 to 11.9), patients with a preexisting opioid use demonstrated significant shorter OS as compared to those who had not used opioids (median OS of 3.6 vs 4.6 years, respectively, P<0.0001, log-rank). Stratified based on the opioid analogue hierarchy, OS was steadily shorter with stronger analgesics demonstrating a median OS of 3.9, 3.9, 3.6, 3.2, 3.2, and 1.8 years in patients who had received codeine, tramadol, pure morphine, oxycodone, buprenorphine, and fentanyl, respectively (Figure 1A; P<0.0001, log-rank). In multivariable analysis adjusting for age, sex, ISS, and presence of MBD at time of diagnosis, the opioid analogue hierarchy demonstrated steadily increasing hazard ratios significant for tramadol, oxycodone, buprenorphine, and fentanyl, whereas presence of MBD lost its prognostic value (Figure 1B). Using the R-ISS instead of ISS produced similar results. Although, the 279 (5.9%) patients with a primary cancer (PC) were more likely to receive opioids compared to those without a PC (164/279 [58.8%] vs 1968/4413 [44.6%], P<0.0001, χ2), OS stratified on the opioid analogue hierarchy was similar after excluding patients with a PC. Summary/Conclusion: In conclusion, the opioid analogue hierarchy may be a valuable prognostic tool indicating that MM patients in pain have shorter OS independent of ISS.Keywords: Prognostic factor, Multiple myeloma, Bone disease